Abstract
In Heteropneustes fossilis, kisspeptins (Kiss) and nonapeptides (NPs; vasotocin, Vt; isotocin, Itb; Val8-isotocin, Ita) stimulate the hypothalamus-pituitary–gonadal (HPG) axis, and estrogen feedback modulates the expression of these systems. In this study, functional interactions among these regulatory systems were demonstrated in the brain and ovary at the mRNA expression level. Human KISS1 (hKISS1) and H. fossilis Kiss2 (HfKiss2) produced biphasic effects on brain and ovarian vt, itb and ita expression at 24 h post injection: low and median doses produced inhibition, no change or mild stimulation, and the highest dose consistently stimulated the mRNA levels. The Kiss peptides produced an upregulation of NP mRNA expression at 24 h incubation of brain and ovarian slices by increasing the concentration of hKISS1 and HfKiss2. The kiss peptides stimulated brain cyp19a1b and ovary cyp19a1a expression, both in vivo and in vitro. Peptide234, a Kiss1 receptor antagonist, inhibited basal mRNA expression of the NPs, cyp19a1b and cyp19a1a, which was prevented by the Kiss peptides, both in vivo and in vitro. In all the experiments, HfKiss2 was more effective than hKISS1 in modulating mRNA expression. The results suggest that the NP and E2 systems are functional targets of Kiss peptides and interact with each other.
Similar content being viewed by others
Data availability
Raw data and materials will be available on request from the lead author.
References
Acharjee A, Chaube R, Joy KP (2018) Reproductive stage- and sex-dependent effects of neurohypophyseal nonapeptides on gonadotropin subunit mRNA expression in the catfish Heteropneustes fossilis: an in vitro study. Gen Comp Endocrinol 260:80–89. https://doi.org/10.1016/j.ygcen.2018.01.001
Balment RJ, Lu W, Weybourne E, Warne JM (2006) Arginine vasotocin, a key hormone in fish physiology and behaviour: a review with insights from mammalian models. Gen Comp Endocrinol 147:9–16. https://doi.org/10.1016/j.ygcen.2005.12.022
Banerjee P, Chaube R, Joy KP (2015) Molecular cloning, sequencing and tissue expression of vasotocin and isotocin precursor genes from Ostariophysian catfishes: phylogeny and evolutionary considerations in teleosts. Front Neurosci 9:166. https://doi.org/10.3389/fnins.2015.00166
Banerjee P, Chaube R, Joy KP (2016) In situ localization of vasotocin and isotocin precursor mRNA in brain and ovary of the catfish Heteropneustes fossilis and estrogen regulation of the gene expression. J Transl Neurosci 1:2
Banerjee P, Chaube R, Joy KP (2018) Molecular cloning and characterization of an isotocin paralogue ([V8] isotocin) in catfishes (superorder Ostariophysi): Origin traced likely to the fish-specific whole genome duplication. J Neuroendocrinol 30:e12647. https://doi.org/10.1111/jne.12647
Biran J, Ben-Dor S, Levavi-Sivan B (2008) Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates. Biol Reprod 79:776–786. https://doi.org/10.1095/biolreprod.107.066266
Callard GV, Tchoudakova AV, Kishida M, Wood E (2001) Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish. J Steroid Biochem Mol Biol 79:305–314. https://doi.org/10.1016/s0960-0760(01)00147-9
Chaube R, Singh RK, Joy KP (2012) Estrogen regulation of brain vasotocin secretion in the catfish Heteropneustes fossilis: an interaction with catecholaminergic system. Gen Comp Endocrinol 175:206–213. https://doi.org/10.1016/j.ygcen.2011.11.012
Chaube R, Rawat A, Joy KP (2015) Molecular cloning and characterization of brain and ovarian cytochrome P450 aromatase genes in the catfish Heteropneustes fossilis: Sex, tissue and seasonal variation in, and effects of gonadotropin on gene expression. Gen Comp Endocrinol 221:120–133. https://doi.org/10.1016/j.ygcen.2015.06.004
Chaube R, Rawat A, Inbaraj RM, Bobe J, Guiguen Y, Fostier A, Joy KP (2017) Identification and characterization of a catechol-o-methyltransferase cDNA in the catfish Heteropneustes fossilis: tissue, sex and seasonal variations, and effects of gonadotropin and 2-hydroxyestradiol-17β on mRNA expression. Gen Comp Endocrinol 246:129–141. https://doi.org/10.1016/j.ygcen.2016.12.001
Chaube R, Sharma S, Senthilkumaran B, Bhat SG, Joy KP (2020) Identification of kisspeptin2 cDNA in the catfish Heteropneustes fossilis: Expression profile, in situ localization and steroid modulation. Gen Comp Endocrinol 294:113472. https://doi.org/10.1016/j.ygcen.2020.113472
Chaube R, Sharma S, Senthilkumaran B, Bhat SG, Joy KP (2022) Kisspeptins stimulate the hypothalamus - pituitary - ovarian axis and induce final oocyte maturation and ovulation in female stinging catfish (Heteropneustes fossilis): evidence from in vivo and in vitro studies. Aquaculture 548:737734. https://doi.org/10.1016/j.aquaculture.2021.737734
Clarkson J, Herbison AE (2006) Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin- releasing hormone neurons. Endocrinology 147:5817–5825
D’Occhio MJ, Campanile G, Baruselli PS (2020) Peripheral action of kisspeptin at reproductive tissues - role in ovarian function and embryo implantation and relevance to assisted reproductive technology in livestock: a review. Biol Reprod 103(6):1157–1170. https://doi.org/10.1093/biolre/ioaa135
de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA 100:10972–10976
Diotel N, DoRego J-L, Anglade I, Vaillant C, Pellegrini E, Vaudry H, Kah O (2011) The brain of teleost fish, a source, and a target of sexual steroids. Front Neurosci 5(137):1–14. https://doi.org/10.3389/fnins.2011.00137
Espigares F, CarrilloGómez MA, Zanuy S (2015) The forebrain-midbrain acts as functional endocrine signaling pathway of Kiss2/Gnrh1 system controlling the gonadotroph activity in the teleost fish European sea bass (Dicentrarchus labrax). Biol Reprod 92(3):1–13. https://doi.org/10.1095/biolreprod.114.125138
Fairgrieve MR, Shibata Y, Smith EK, Hayman ES, Luckenbach JA (2016) Molecular characterization of the gonadal kisspeptin system: cloning, tissue distribution, gene expression analysis and localization in sablefish (Anoplopoma fimbria). Gen Comp Endocrinol 225:212–223
Filby AL, Aerle RV, Duitman J, Tyler CR (2008) The kisspeptin/gonadotropin-releasing hormone pathway and molecular signaling of puberty in fish. Biol Reprod 78(2):278–289. https://doi.org/10.1095/biolreprod.107.063420
Forlano PM, Deitcher DL, Myers DA, Bass AH (2001) Anatomical distribution and cellular basis for high levels of aromatase activity in the brain of teleost fish: aromatase enzyme and mRNA expression identify glia as source. J Neurosci 21(22):8943–8955
Gaytan F, Gaytan M, Castellano JM, Romero M, Roa J, Aparicio B et al (2009) KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction. Am J Physiol Endocrinol Metab 296:E520–E531. https://doi.org/10.1152/ajpendo.90895.2008
Goodson JL, Thompson RR (2010) Nonapeptide mechanisms of social cognition, behavior and species-specific social systems. Curr Opin Neurobiol 20:784–794. https://doi.org/10.1016/j.conb.2010.08.020
Gopurappilly R, Ogawa S, Parhar IS (2013) Functional significance of GnRH and kisspeptin, and their cognate receptors in teleost reproduction. Front Endocrinol 4:24. https://doi.org/10.3389/fendo.2013.00024
Hawkins MB, Godwin J, Crews D, Thomas P (2005) The distributions of the duplicate oestrogen receptors ER-βa and ER-βb in the forebrain of the Atlantic croaker (Micropogonias undulatus): evidence for subfunctionalization after gene duplication. PRoc Biol Sci 272(1563):633–641. https://doi.org/10.1098/rspb.2004.3008
Hrabovszky E (2014) Neuroanatomy of the human hypothalamic kisspeptin system. Neuroendocrinology 99:33–48
Hu KL, Zhao H, Chang HM, Yu Y, Qiao J (2018) Kisspeptin/Kisspeptin receptor system in the ovary. Front Endocrinol 8:365. https://doi.org/10.3389/fendo.2017.00365
Joy KP, Chaube R (2015) Vasotocin – A new player in the control of oocyte maturation and ovulation in fish. Gen Comp Endocrinol 196:91–99. https://doi.org/10.1016/j.ygcen.2015.02.013
Kanda S, Akazome Y, Matsunaga T, Yamamoto N, Yamada S et al (2008) Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (Oryzias latipes). Endocrinology 149:2467–2476
Kanda S, Akazome Y, Mitani Y, Okubo K, Oka Y (2013) Neuroanatomical evidence that kisspeptin directly regulates isotocin and vasotocin neurons. PLoS ONE 8(4):e62776. https://doi.org/10.1371/journal.pone.0062776
Kazeto Y, Ijiri S, Place AR, Zohar Y, Trant JM (2001) The 5’ flanking regions of CYP19A1 and CYP19A2 in zebrafish. Biochem Biophys Res Commun 288:503–508
Klenke U, Zmora N, Stubblefield J, Zohar Y (2011) Expression patterns of the kisspeptin system and GnRH1 correlate in their response to gonadal feedback in female striped bass. Indian J Sci Technol 4:33–34
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM et al (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276:34631–34636
Kumari P, Sehgal N (2020) Heteropneustes fossilis kisspeptin 1 (KISS1) mRNA, partial cds GenBank: MN970146.1
Lee YR, Tsunekawa K, Moon MJ, Um HN, Hwang JI, Osugi T, Otaki N, Sunakawa Y, Kim K, Vaudry H, Kwon HB, Seong JY, Tsutsui K (2009) Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology 150:2837–2846. https://doi.org/10.1210/en.2008-1679
Lehman MN, Coolen LM, Goodman RL (2010) Minireview: Kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology 151:3479–3489. https://doi.org/10.1210/en.2010-0022
Li S, Zhang Y, Liu Y, Huang X, Huang W, Lu D, Lin H (2009) Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus). J Endocrinol 201:407–418. https://doi.org/10.1677/JOE-09-0016
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real time quantitative PCR and the 2-DDCT method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
Marsh KE, Creutz LM, Hawkins MB, Godwin J (2006) Aromatase immunoreactivity in the bluehead wrasse brain, Thalassoma bifasciatum: immunolocalization and coregionalization with arginine vasotocin and tyrosine hydroxylase. Brain Res 1126(1):91–101
Menuet A, Anglade I, Le Guevel R, Pellegrini E, Pakdel F, Kah O (2003) Distribution of aromatase mRNA and protein in the brain and pituitary of female rainbow trout: comparison with estrogen receptor alpha. J Comp Neurol 462(2):180–193. https://doi.org/10.1002/cne.10726
Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MB et al (2005) Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor. Proc Natl Acad Sci 102:1761–1766
Mishra S, Chaube R (2016) Localization of P450 aromatase in the brain of adult catfish Heteropneustes fossilis and regional distribution of estradiol-17b and testosterone: gender and seasonal differences. J Neurol Neurosci 7:77
Mitani Y, Kanda S, Akazome Y, Zempo B, Oka Y (2010) Hypothalamic Kiss1 but not Kiss2 neurons are involved in estrogen feedback in medaka (Oryzias latipes). Endocrinology 151:1751–1759
Muriach B, Cerdá-Reverter JM, Gómez A, Zanuy S, Carrillo M (2008) Molecular characterization and central distribution of the estradiol receptor alpha (ERalpha) in the sea bass (Dicentrarchus labrax). J Chem Neuroanat 35(1):33–48. https://doi.org/10.1016/j.jchemneu.2007.05.010
Navarro VM, Castellano JM, McConkey SM, Pineda R, Ruiz-Pino F, Pinilla L, Clifton DK, Tena-Sempere M, Steiner RA (2011) Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab 300:E202–E210. https://doi.org/10.1152/ajpendo.00517.2010
Oakley AE, Clifton DK, Steiner RA (2009) Kisspeptin signaling in the brain. Endocr Rev 30:713–743
Ohga H, Selvaraj S, Matsuyama M (2018) The roles of kisspeptin system in the reproductive physiology of fish with special reference to chub mackerel studies as main axis. Front Endocrinol 9:147. https://doi.org/10.3389/fendo.2018.00147
Pasquier J, Lafont AG, Tostivint H, Vaudry H, Rousseau K, Dufour S (2012) Comparative evolutionary histories of kisspeptins and kisspeptin receptors in vertebrates reveal both parallel and divergent features. Front Endocrinol 3:173. https://doi.org/10.3389/fendo.2012.00173
Piferrer F, Blázquez M (2005) Aromatase distribution and regulation in fish. Fish Physiol Biochem 31:215–226. https://doi.org/10.1007/s10695-006-0027-0
Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M (2012) Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev 92:1235–1316. https://doi.org/10.1152/physrev.00037.2010
Roseweir AK, Kauffman AS, Smith JT, Guerriero KA, Morgan K et al (2009) Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J Neurosci 29(12):3920–3929. https://doi.org/10.1523/JNEUROSCI.5740-08.2009
Ruohonen ST, Gaytan F, Gaudi AU, Velasco I, Kukoricza K et al (2022) Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure. Human Reprod 37(4):806–821. https://doi.org/10.1093/humrep/deab287
Scott V, Brown CH (2011) Kisspeptin activation of supraoptic nucleus neurons in vivo. Endocrinology 152:3862–3870. https://doi.org/10.1210/en.2011-1181
Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O’Rahilly S, Carlton MB, Crowley WF Jr, Aparicio SA, Colledge WH (2003) The GPR54 gene as a regulator of puberty. New Engl J Med 349:1614–1627
Servili A, Le Page Y, Leprince J, Caraty A, Escobar S, Parhar IS, Seong JY, Vaudry H, Kah O (2011) Organization of two independent kisspeptin systems delivered from evolutionary-ancient kiss genes in the brain of zebrafish. Endocrinology 152:1527–1540. https://doi.org/10.1210/en.2010-0948
Singh V, Joy KP (2008) Immunocytochemical localization, HPLC characterization, and seasonal dynamics of vasotocin in the brain, blood plasma and gonads of the catfish Heteropneustes fossilis. Gen Comp Endocrinol 159:214–225
Singh V, Joy KP (2009) Relative in vitro seasonal effects of vasotocin and isotocin on ovarian steroid hormone levels in the catfish Heteropneustes fossilis. Gen Comp Endocrinol 162:257–264. https://doi.org/10.1016/j.ygcen.2009.03.024
Singh V, Joy KP (2011) Vasotocin induces final oocyte maturation and ovulation through the production of a maturation-inducing steroid in the catfish Heteropneustes fossilis. Gen Comp Endocrinol 174:15–21. https://doi.org/10.1016/j.ygcen.2011.07.009
Singh V, Joy KP (2013) Functional interactions between vasotocin and prostaglandins during final oocyte maturation and ovulation in the catfish Heteropneustes fossilis. Gen Comp Endocrinol 186(2013):126–135. https://doi.org/10.1016/j.ygcen.2013.02.043
Singh A, Lal B, Parkash J, Millar RP (2021) Gametogenic and steroidogenic action of kisspeptin-10 in the Asian catfish, Clarias batrachus: Putative underlying mechanistic cascade. Comp Biochem Physiol, Part B 256:110642. https://doi.org/10.1016/j.cbpb.2021.110642
Sivalingam M, Parhar IS (2022) Hypothalamic kisspeptin and kisspeptin receptors: species variation in reproduction and reproductive behaviours. Front Neuroendocrinol 64:100951. https://doi.org/10.1016/j.yfrne.2021.100951
Sobrino V, Avendano MS, Perdices-Lopez C, Jimenez-Puyer M, Tena-Sempere M (2022) Kisspeptins and the neuroendocrine control of reproduction: Recent progress and new frontiers in kisspeptin research. Front Neuroendocrinol 65:100977. https://doi.org/10.1016/j.yfrne.2021.100977
Somoza GM, Mechaly AS, Trudeau VL (2020) Kisspeptin and GnRH interactions in the reproductive brain of teleosts. Gen Comp Endocrinol 298:113568. https://doi.org/10.1016/j.ygcen.2020.113568
Song Y, Duan X, Chen J, Huang W, Zhu Z, Hu W (2015) The distribution of kisspeptin (kiss) 1-and kiss2-positive neurones and their connections with gonadotrophin-releasing hormone-3 neurones in the zebrafish brain. J Neuroendocrinol 27(3):198–211. https://doi.org/10.1111/jne.12251
Song Y, Chen J, Tao B, Luo D, Zhu Z, Hu W (2020) Kisspeptin2 regulates hormone expression in female zebrafish (Danio rerio) pituitary. Mol Cell Endocrinol 513:110858. https://doi.org/10.1016/j.mce.2020.110858
Ten SC, Gu SY, Niu YF, An XF, Yan M, He M (2010) Central administration of kisspeptin-10 inhibits water and sodium excretion of anaesthetized male rats and the involvement of arginine vasopressin. Endocr Res 35:128–136
Terasawa E (2018) Neuroestradiol in regulation of GnRH release. Horm Behav 104:138–145. https://doi.org/10.1016/j.yhbeh.2018.04.003
Wang L, Moenter SM (2020) Differential roles of hypothalamic AVPV and arcuate kisspeptin neurons in estradiol feedback regulation of female reproduction. Neuroendocrinology 110:172–184. https://doi.org/10.1159/000503006
Wang B, Mechaly AS, Somoza GM (2022) Overview and new insights into the diversity, evolution, role, and regulation of kisspeptins and their receptors in teleost fish. Front Endocrinol 13:862614. https://doi.org/10.3389/fendo.2022.862614
Yilmaz MB, Oksuz H (2019) The role of kisspeptin on aromatase expression in breast cancer. Bratislava Med J 119(12):776–780. https://doi.org/10.4149/BLL_2018_141
Zhang H, Zhang B, Qin G, Li S, Lin Q (2018) The roles of the kisspeptin system in the reproductive physiology of the lined seahorse (Hippocampus erectus), an ovoviviparous fish with male pregnancy. Front Neurosci 12:940. https://doi.org/10.3389/fnins.2018.00940
Zmora N, Stubblefield J, Zulperi Z, Biran J, Levavi-Sivan B, Muñoz-Cueto JA, Zohar Y (2012) Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, morone species. Biol Reprod 86(6):177. https://doi.org/10.1095/biolreprod.111.097667
Zmora N, Stubblefield JD, Wong T-T, Levavi-Sivan B, Millar RP, Zohar Y (2015) Kisspeptin antagonists reveal kisspeptin 1 and kisspeptin 2 differential regulation of reproduction in the. Biol Reprod 93(3):76. https://doi.org/10.1095/biolreprod.115.131870. (1–12)
Acknowledgements
The research was partly supported by grants from the Department of Science and Technology, New Delhi (Fund for Improvement of S & T Infrastructure) and Banaras Hindu University, Varanasi (Institute of Excellence) to the Department of Zoology. The authors are thankful to BHU-Department of Biotechnology, New Delhi – Interdisciplinary School of Life Science for the qPCR facility.
Funding
No specific funding is involved in this study other than that mentioned under.
Author information
Authors and Affiliations
Contributions
RC and KPJ designed the experiments. SS conducted the experiments and collated and analysed the data. RC reanalysed the data and prepared the initial draft. KPJ finalized the writing of the manuscript. All the authors read, corrected and approved the final version of the manuscript for publication.
Ethics declarations
Ethical approval
The experiments were conducted according to the guidelines of the Animal Ethics Committee of Banaras Hindu University, Varanasi.
Consent to participate
Not applicable
Consent for publication
Not applicable.
Competing interests
RC and SS declare no potential conflict of interest. KPJ is an Editor on the journal Fish Physiology and Biochemistry Editorial Board and has received compensation from the publisher.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Chaube, R., Sharma, S. & Joy, K. Kisspeptin modulation of nonapeptide and cytochrome P450 aromatase mRNA expression in the brain and ovary of the catfish Heteropneustes fossilis: in vivo and in vitro studies. Fish Physiol Biochem 49, 1489–1509 (2023). https://doi.org/10.1007/s10695-023-01270-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-023-01270-w